Lychnopholide loaded in surface modified polylactide nanocapsules (LYC-PLA-PEG-NC) cure mice infected by Trypanosoma cruzi strain a prototype of resistance to benznidazole and nifurtimox: First insights of its mechanism of action

Chagas disease (CD) remains neglected and causes high morbidity and mortality. The great difficulty is the lack of effective treatment. The current drugs cause side effects and have limited therapeutic efficacy in the chronic phase. This study aims to fulfil some gaps in studies of the natural subst...

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Published in:Experimental parasitology 2023-12, Vol.255, p.108647-108647, Article 108647
Main Authors: Milagre, Matheus Marques, Torchelsen, Fernanda Karoline Vieira da Silva, Pedrosa, Tamiles Caroline Fernandes, Teixeira, Gabriel Marques, Sampaio, Larissa Silva, Saúde-Guimarães, Dênia Antunes, Branquinho, Renata Tupinambá, Mosqueira, Vanessa Carla Furtado, Lana, Marta de
Format: Article
Language:English
Subjects:
Animals
Chagas Disease - drug therapy
Mice
Nanocapsules
Nifurtimox - therapeutic use
Nitroimidazoles - pharmacology
Nitroimidazoles - therapeutic use
Polyesters - pharmacology
Polyesters - therapeutic use
Trypanocidal Agents - pharmacology
Trypanocidal Agents - therapeutic use
Trypanosoma cruzi
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Summary:Chagas disease (CD) remains neglected and causes high morbidity and mortality. The great difficulty is the lack of effective treatment. The current drugs cause side effects and have limited therapeutic efficacy in the chronic phase. This study aims to fulfil some gaps in studies of the natural substance lychnopholide nanoencapsulated LYC-PLA-PEG-NC (LYC-NC) and free (Free-LYC): the activity in epimastigotes and amastigotes to determine its selectivity index (SI), the therapeutic efficacy in mice infected with Colombian Trypanosoma cruzi strain and insight of the mechanism of LYC-NC action on T. cruzi. The SI was obtained by calculation of the ratio between the IC value toward H9c2 cells divided by the IC value in the anti-T. cruzi test. Infected Swiss mice were treated with 2 and 12 mg/kg/day via intravenous and oral, respectively, and the therapeutic efficacy was determined. The IC of LYC-NC and Free-LYC for epimastigotes of T. cruzi were similar. Both were active against amastigotes in cell culture, particularly Free-LYC. The SI of LYC-NC and Free-LYC were 45.38 and 32.11, respectively. LYC-NC 2 and 12 mg/kg/day cured parasitologically, 62.5% and 80% of the animals, respectively, infected with a strain resistant to treatment. The fluorescent NC was distributed in the cardiomyocyte cytoplasm, infected or not, and interacted with the trypomastigotes. Together, these results represent advances in demonstrating LYC as a potent new therapeutic option for treating CD.
ISSN:0014-4894
1090-2449
DOI:10.1016/j.exppara.2023.108647